Bomedemstat (IMG-7289/MK-3543) in Participants With Myelofibrosis (IMG-7289-CTP-102/MK-3543-002)

NCT03136185 — Phase 1 / Phase 2, Completed, 90 participants, Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc., (Rahway, New Jersey USA)

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A Multi-Center, Open Label Study to Assess the Safety, Steady-State Pharmacokinetics and Pharmacodynamics of IMG-7289 in Patients With Myelofibrosis

Registry	NCT03136185
Status	Completed
Phase	Phase 1 / Phase 2
Study type	Interventional; non randomized, single group, masking: none, treatment
Enrollment	90 (Actual)
Sponsor	Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc., (Rahway, New Jersey USA) (Industry)
Conditions	Myelofibrosis, Post-polycythemia Vera Myelofibrosis (PPV-MF), Post-essential Thrombocythemia Myelofibrosis (PET-MF), Primary Myelofibrosis (PMF)
Interventions	Bomedemstat (Drug)
Dates	start 2017-07-18, primary completion 2022-03-08, completion 2022-03-08, first posted 2017-05-02, last updated 2024-01-10
Locations	5 sites in United States, Australia, Germany, Italy, United Kingdom

-Summary

This is a Phase 1/2 open-label study to evaluate the safety, tolerability, steady-state pharmacokinetic (PK) and pharmacodynamics (PD) of a lysine-specific demethylase 1 (LSD1) inhibitor, bomedemstat (IMG-7289/MK-3543), administered orally once daily in participants with myelofibrosis.

The primary hypothesis is that bomedemstat is a safe and tolerable orally available agent when administered to participants with myelofibrosis including primary myelofibrosis (PMF), post-polycythaemia vera-myelofibrosis (PPVMF), and post-essential thrombocythaemia-myelofibrosis (PET-MF) (collectively referred to as 'MF'); inhibition of LSD1 by bomedemstat will reduce spleen size in those with splenomegaly, improve haematopoiesis and reduce constitutional symptoms associated with these disorders.

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+Detailed description

This study initiated as a Phase 1/2a study assessing the safety of the starting dose, an 85-day duration of treatment, and the PK and PD effects of bomedemstat, with transition to a Phase 2b study incorporating changes supported by the Phase 1/2a data.

+Arms and interventions

Arm	Type	Interventions	Description
Ph 1/2a PMF: Bomedemstat 0.25 mg/kg/d	Experimental	Drug: Bomedemstat	In the Phase 1/2a portion of the study, PMF participants received 0.25 mg/kg/d bomedemstat orally every day (qd) for 85 days during the Initial Treatment Period (ITP). Qualifying participants could continue to receive treatment for an additional 85 days during an Additional Treatment Period (ATP) as determined by the investigator. The ATP could repeat indefinitely in participants that continued to derive clinical benefit.
Ph 1/2a PPV-MF: Bomedemstat 0.25 mg/kg/d	Experimental	Drug: Bomedemstat	In the Phase 1/2a portion of the study, PPV-MF participants received 0.25 mg/kg/d bomedemstat orally qd for 85 days during the ITP. Qualifying participants could continue to receive treatment for an additional 85 days during an ATP as determined by the investigator. The ATP could repeat indefinitely in participants that continued to derive clinical benefit.
Ph 1/2a PET-MF: Bomedemstat 0.25 mg/kg/d	Experimental	Drug: Bomedemstat	In the Phase 1/2a portion of the study, PET-MF participants received 0.25 mg/kg/d bomedemstat orally qd for 85 days during the ITP. Qualifying participants could continue to receive treatment for an additional 85 days during an ATP as determined by the investigator. The ATP could repeat indefinitely in participants that continued to derive clinical benefit.
Ph 2b PMF: Bomedemstat 0.5 mg/kg/d	Experimental	Drug: Bomedemstat	In the Phase 2b portion of the study, PMF participants received 0.5 mg/kg/d bomedemstat orally qd for 169 days during the ITP. Qualifying participants could continue to receive treatment for an additional 169 days during an ATP as determined by the investigator. The ATP could repeat indefinitely in participants that continued to derive clinical benefit.
Ph 2b PPV-MF: Bomedemstat 0.5 mg/kg/d	Experimental	Drug: Bomedemstat	In the Phase 2b portion of the study, PPV-MF participants received 0.5 mg/kg/d bomedemstat orally qd for 169 days during the ITP. Qualifying participants could continue to receive treatment for an additional 169 days during an ATP as determined by the investigator. The ATP could repeat indefinitely in participants that continued to derive clinical benefit.
Ph 2b PET-MF: Bomedemstat 0.5 mg/kg/d	Experimental	Drug: Bomedemstat	In the Phase 2b portion of the study, PET-MF participants received 0.5 mg/kg/d bomedemstat orally qd for 169 days during the ITP. Qualifying participants could continue to receive treatment for an additional 169 days during an ATP as determined by the investigator. The ATP could repeat indefinitely in participants that continued to derive clinical benefit.
Ph 2b PMF: Bomedemstat 0.6 mg/kg/d	Experimental	Drug: Bomedemstat	In the Phase 2b portion of the study, PMF participants received 0.6 mg/kg/d bomedemstat orally qd for 169 days during the ITP. Qualifying participants could continue to receive treatment for an additional 169 days during an ATP as determined by the investigator. The ATP could repeat indefinitely in participants that continued to derive clinical benefit.
Ph 2b PPV-MF: Bomedemstat 0.6 mg/kg/d	Experimental	Drug: Bomedemstat	In the Phase 2b portion of the study, PPV-MF participants received 0.6 mg/kg/d bomedemstat orally qd for 169 days during the ITP. Qualifying participants could continue to receive treatment for an additional 169 days during an ATP as determined by the investigator. The ATP could repeat indefinitely in participants that continued to derive clinical benefit.
Ph 2b PET-MF: Bomedemstat 0.6 mg/kg/d	Experimental	Drug: Bomedemstat	In the Phase 2b portion of the study, PET-MF participants received 0.6 mg/kg/d bomedemstat orally qd for 169 days during the ITP. Qualifying participants could continue to receive treatment for an additional 169 days during an ATP as determined by the investigator. The ATP could repeat indefinitely in participants that continued to derive clinical benefit.

Bomedemstat (Drug), also known as IMG-7289, MK-3543, LSD1 inhibitor: Oral (capsule) administration according to dose allocation.

+Outcome measures

Primary outcomes

Number of Participants With Dose Limiting Toxicities (DLTs) [Up to Day 7 of the ITP]: DLT was defined as any one of the following adverse events (AEs) that occured through Day 7 of the Initial Treatment Period (ITP) and was considered by the Investigator to be possibly, probably or definitely related to bomedemstat: * Thrombocytopenia leading to clinically significant sequelae (i.e., a clinically significant bleeding event or the need for prophylactic transfusions) * A clinically significant bleeding event in a participant with a platelet count >50 x 10\^9/L (50 k/μL) * Any Grade 4 or 5 non-haematologic adverse event * Any Grade 3 non-haematologic adverse event with failure to recover to Grade 2 within 7 days of drug cessation, with the following exceptions: ≥ Grade 3 nausea, vomiting or diarrhea that responds to standard medical care; ≥ Grade 3 aesthenia lasting less than 14 days; any Grade 3 electrolyte abnormality unrelated to the underlying malignancy and persisting greater than 24 hours. The number of participants with a DLT were reported.
Number of Participants With Serious Adverse Events [Up to approximately 30 months]: An AE was any undesirable physical, psychological or behavioral effect experienced by a participant, in conjunction with the use of the drug or biologic, whether or not product-related. This included any untoward signs or symptoms experienced by the participant from the time of first dose with bomedemstat until completion of the study. Serious AEs (SAEs) were any AE that resulted in death, life-threatening experience, required or prolonged inpatient hospitalization, persistent or significant disability/incapacity, congenital anomaly, or important medical events. The number of participants with at least one treatment-emergent (TE) SAE was reported for each arm.
Number of Participants With Adverse Events [Up to approximately 30 months]: An AE was any undesirable physical, psychological or behavioral effect experienced by a participant, in conjunction with the use of the drug or biologic, whether or not product-related. This included any untoward signs or symptoms experienced by the participant from the time of first dose with bomedemstat until completion of the study. The number of participants with at least one TE AE was reported for each arm.
Number of Participants That Discontinued Study Treatment Due To AEs [Up to approximately 29 months]: An AE was any undesirable physical, psychological or behavioral effect experienced by a participant, in conjunction with the use of the drug or biologic, whether or not product-related. This included any untoward signs or symptoms experienced by the participant from the time of first dose with bomedemstat until completion of the study. The number of participants that discontinued study treatment with bomedemstat due to a TE AE was reported for each arm.
Phase 1/2a Portion: Observed Maximum Concentration (Cmax) of Bomedemstat [Day 21: Pre-dose and 0.5, 1, 2, 3, 4, 8, and 24 hours (Day 22) after dosing.]: Cmax was defined as the maximum observed concentration after administration obtained directly from the concentration time profile. Blood and plasma samples were collected at pre-specified timepoints to calculate Cmax in participants of the Phase 1/2a portion of the study. As pre-specified by the protocol and Pharmacokinetic Analysis Plan (PAP), Phase 2b participants were excluded from this analysis.
Phase 1/2a Portion: Time to Maximum Concentration (Tmax) of Bomedemstat [Day 21: Pre-dose and 0.5, 1, 2, 3, 4, 8, and 24 hours (Day 22) after dosing.]: Tmax was defined as the time to maximum concentration after administration obtained by inspection. Blood and plasma samples were collected at pre-specified timepoints to calculate Tmax in participants of the Phase 1/2a portion of the study. As pre-specified by the protocol and Pharmacokinetic Analysis Plan (PAP), Phase 2b participants were excluded from this analysis.
Phase 1/2a Portion: Area Under the Concentration-time Curve of Bomedemstat From Time 0 to 24 Hours Post-dose (AUC0-24) [Day 21: Pre-dose and 0.5, 1, 2, 3, 4, 8, and 24 hours (Day 22) after dosing.]: AUC0-24 was defined as the area under the concentration versus time curve calculated using the linear trapezoidal rule from the zero time-point to the 24-hour time-point concentration. Blood and plasma samples were collected at pre-specified timepoints to calculate AUC0-24 in participants of the Phase 1/2a portion of the study. As pre-specified by the protocol and Pharmacokinetic Analysis Plan (PAP), Phase 2b participants were excluded from this analysis.
Phase 1/2a Portion: Apparent Total Clearance (CL/F) of Bomedemstat After Oral Administration [Day 21: Pre-dose and 0.5, 1, 2, 3, 4, 8, and 24 hours (Day 22) after dosing.]: CL/F was defined as the apparent total clearance of drug after oral administration. Blood and plasma samples were collected at pre-specified timepoints to calculate CL/F in participants of the Phase 1/2a portion of the study. As pre-specified by the protocol and Pharmacokinetic Analysis Plan (PAP), Phase 2b participants were excluded from this analysis.
Percentage Change From Baseline in Spleen Volume [Baseline, ITP Day 84 (Study Day 84), ITP Day 168 (Study Day 168), ATP1 Day 84 (Study Day 253), and ATP1 Day 168 (Study Day 337)]: Change in spleen volume was assessed based on calculated spleen volume (ml) measured by magnetic resonance imaging (MRI), or computerized tomography (CT) scan (where locally permitted) if the participant was not a candidate for MRI from Day 0. Percentage change from baseline in spleen volume was reported at Initial Treatment Period (ITP) Day 84, ITP Day 168, Additional Treatment Period 1 (ATP1) Day 84 (Study Day 253), and ATP1 Day 168 (Study Day 337).
Percentage Change From Baseline in Spleen Size [Baseline, ITP Day 84 (Study Day 84), ITP Day 168 (Study Day 168), ATP1 Day 84 (Study Day 253), ATP1 Day 168 (Study Day 337), ATP2 Day 84 (Study Day 422), ATP2 Day 168 (Study Day 506), and ATP3 Day 84 (Study Day 591)]: Change in spleen size was assessed based on spleen palpation (in cm) at each visit. Percentage change from baseline in spleen size was reported at ITP Day 84, ITP Day 168, ATP1 Day 84 (Study Day 253), ATP1 Day 168 (Study Day 337), ATP2 Day 84 (Study Day 422), ATP2 Day 168 (Study Day 506), and ATP3 Day 84 (Study Day 591). As prespecified by the Statistical Analysis Plan, assessments for the Phase 1/2 groups were summarized using visit windowing after the Day 84 visit of the ITP to allow for comparison with the Phase 2b groups at ITP Day 168.

+Eligibility

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* >18 years of age
* Diagnosis of either PMF per World Health Organization (WHO) diagnostic criteria for myeloproliferative neoplasms, or PPV-MF or PET-MF per the International Working Group for Myelofibrosis Research and Treatment
* High or intermediate-2 risk disease

Exclusion Criteria:

* Receiving other treatments for the condition (with exceptions and time limits)
* Major surgery in last 4 weeks, any surgery in the last 2 weeks
* History of, or scheduled, hematopoietic stem cell transplant within 24 weeks of Screening
* History of splenectomy
* Current use of prohibited medications
* A concurrent second active and nonstable malignancy
* Known human immunodeficiency virus infection or active Hepatitis B or Hepatitis C virus infection
* Other hematologic/biochemistry requirements, as per protocol
* Use of an investigational agent within last 14 days
* Pregnant or lactating females

+Posted results

Participant flow

Milestone	Ph 1/2a PMF: Bomedemstat 0.25 mg/kg/d	Ph 1/2a PPV-MF: Bomedemstat 0.25 mg/kg/d	Ph 1/2a PET-MF: Bomedemstat 0.25 mg/kg/d	Ph 2b PMF: Bomedemstat 0.5 mg/kg/d	Ph 2b PPV-MF: Bomedemstat 0.5 mg/kg/d	Ph 2b PET-MF: Bomedemstat 0.5 mg/kg/d	Ph 2b PMF: Bomedemstat 0.6 mg/kg/d	Ph 2b PPV-MF: Bomedemstat 0.6 mg/kg/d	Ph 2b PET-MF: Bomedemstat 0.6 mg/kg/d
Started	9	3	6	8	5	11	24	11	13
Treated	9	3	6	8	5	11	24	11	13
Entered additional treatment period (atp)	6	2	3	3	1	4	17	5	9
Completed initial treatment period (itp)	7	3	4	4	1	4	18	8	10
Completed	1	0	0	2	0	3	14	5	7
Not completed	8	3	6	6	5	8	10	6	6

Outcome results

Number of Participants With Dose Limiting Toxicities (DLTs) (Primary), Count of participants, Participants: Ph 1/2a PMF: Bomedemstat 0.25 mg/kg/d 0; Ph 1/2a PPV-MF: Bomedemstat 0.25 mg/kg/d 0; Ph 1/2a PET-MF: Bomedemstat 0.25 mg/kg/d 0; Ph 2b PMF: Bomedemstat 0.5 mg/kg/d 0; Ph 2b PPV-MF: Bomedemstat 0.5 mg/kg/d 0; Ph 2b PET-MF: Bomedemstat 0.5 mg/kg/d 0; Ph 2b PMF: Bomedemstat 0.6 mg/kg/d 0; Ph 2b PPV-MF: Bomedemstat 0.6 mg/kg/d 0; Ph 2b PET-MF: Bomedemstat 0.6 mg/kg/d 0
Number of Participants With Serious Adverse Events (Primary), Count of participants, Participants: Ph 1/2a PMF: Bomedemstat 0.25 mg/kg/d 4; Ph 1/2a PPV-MF: Bomedemstat 0.25 mg/kg/d 2; Ph 1/2a PET-MF: Bomedemstat 0.25 mg/kg/d 5; Ph 2b PMF: Bomedemstat 0.5 mg/kg/d 4; Ph 2b PPV-MF: Bomedemstat 0.5 mg/kg/d 4; Ph 2b PET-MF: Bomedemstat 0.5 mg/kg/d 7; Ph 2b PMF: Bomedemstat 0.6 mg/kg/d 12; Ph 2b PPV-MF: Bomedemstat 0.6 mg/kg/d 3; Ph 2b PET-MF: Bomedemstat 0.6 mg/kg/d 3
Number of Participants With Adverse Events (Primary), Count of participants, Participants: Ph 1/2a PMF: Bomedemstat 0.25 mg/kg/d 9; Ph 1/2a PPV-MF: Bomedemstat 0.25 mg/kg/d 3; Ph 1/2a PET-MF: Bomedemstat 0.25 mg/kg/d 6; Ph 2b PMF: Bomedemstat 0.5 mg/kg/d 8; Ph 2b PPV-MF: Bomedemstat 0.5 mg/kg/d 5; Ph 2b PET-MF: Bomedemstat 0.5 mg/kg/d 11; Ph 2b PMF: Bomedemstat 0.6 mg/kg/d 23; Ph 2b PPV-MF: Bomedemstat 0.6 mg/kg/d 10; Ph 2b PET-MF: Bomedemstat 0.6 mg/kg/d 12
Number of Participants That Discontinued Study Treatment Due To AEs (Primary), Count of participants, Participants: Ph 1/2a PMF: Bomedemstat 0.25 mg/kg/d 0; Ph 1/2a PPV-MF: Bomedemstat 0.25 mg/kg/d 1; Ph 1/2a PET-MF: Bomedemstat 0.25 mg/kg/d 5; Ph 2b PMF: Bomedemstat 0.5 mg/kg/d 1; Ph 2b PPV-MF: Bomedemstat 0.5 mg/kg/d 2; Ph 2b PET-MF: Bomedemstat 0.5 mg/kg/d 4; Ph 2b PMF: Bomedemstat 0.6 mg/kg/d 5; Ph 2b PPV-MF: Bomedemstat 0.6 mg/kg/d 2; Ph 2b PET-MF: Bomedemstat 0.6 mg/kg/d 3
Phase 1/2a Portion: Observed Maximum Concentration (Cmax) of Bomedemstat (Primary), Geometric mean, ng/mL: Ph 1/2a Portion: Bomedemstat 0.25 mg/kg/d 12.63 +/- 104.41; Ph 2b PMF: Bomedemstat 0.5 mg/kg/d ; Ph 2b PPV-MF: Bomedemstat 0.5 mg/kg/d ; Ph 2b PET-MF: Bomedemstat 0.5 mg/kg/d ; Ph 2b PMF: Bomedemstat 0.6 mg/kg/d ; Ph 2b PPV-MF: Bomedemstat 0.6 mg/kg/d ; Ph 2b PET-MF: Bomedemstat 0.6 mg/kg/d
Phase 1/2a Portion: Time to Maximum Concentration (Tmax) of Bomedemstat (Primary), Median, hour: Ph 1/2a Portion: Bomedemstat 0.25 mg/kg/d 1.00 (0.50 to 2.85); Ph 2b PMF: Bomedemstat 0.5 mg/kg/d ; Ph 2b PPV-MF: Bomedemstat 0.5 mg/kg/d ; Ph 2b PET-MF: Bomedemstat 0.5 mg/kg/d ; Ph 2b PMF: Bomedemstat 0.6 mg/kg/d ; Ph 2b PPV-MF: Bomedemstat 0.6 mg/kg/d ; Ph 2b PET-MF: Bomedemstat 0.6 mg/kg/d
Phase 1/2a Portion: Area Under the Concentration-time Curve of Bomedemstat From Time 0 to 24 Hours Post-dose (AUC0-24) (Primary), Geometric mean, hour•ng/mL: Ph 1/2a Portion: Bomedemstat 0.25 mg/kg/d 63.90 +/- 68.56; Ph 2b PMF: Bomedemstat 0.5 mg/kg/d ; Ph 2b PPV-MF: Bomedemstat 0.5 mg/kg/d ; Ph 2b PET-MF: Bomedemstat 0.5 mg/kg/d ; Ph 2b PMF: Bomedemstat 0.6 mg/kg/d ; Ph 2b PPV-MF: Bomedemstat 0.6 mg/kg/d ; Ph 2b PET-MF: Bomedemstat 0.6 mg/kg/d
Phase 1/2a Portion: Apparent Total Clearance (CL/F) of Bomedemstat After Oral Administration (Primary), Geometric mean, mL/min: Ph 1/2a Portion: Bomedemstat 0.25 mg/kg/d 12787.43 +/- 63.72; Ph 2b PMF: Bomedemstat 0.5 mg/kg/d ; Ph 2b PPV-MF: Bomedemstat 0.5 mg/kg/d ; Ph 2b PET-MF: Bomedemstat 0.5 mg/kg/d ; Ph 2b PMF: Bomedemstat 0.6 mg/kg/d ; Ph 2b PPV-MF: Bomedemstat 0.6 mg/kg/d ; Ph 2b PET-MF: Bomedemstat 0.6 mg/kg/d
Percentage Change From Baseline in Spleen Volume (Primary), Mean, Percentage Change: Ph 1/2a PMF: Bomedemstat 0.25 mg/kg/d 3.3 (-50.5 to 57.0); Ph 1/2a PPV-MF: Bomedemstat 0.25 mg/kg/d -13.7 (-49.6 to 22.2); Ph 1/2a PET-MF: Bomedemstat 0.25 mg/kg/d 2.2 (-110.3 to 114.8); Ph 2b PMF: Bomedemstat 0.5 mg/kg/d -9.1 (-27.9 to 9.6); Ph 2b PPV-MF: Bomedemstat 0.5 mg/kg/d -7.2 (-80.2 to 65.8); Ph 2b PET-MF: Bomedemstat 0.5 mg/kg/d 0.3 (-32.3 to 32.9); Ph 2b PMF: Bomedemstat 0.6 mg/kg/d 10.0 (1.2 to 18.8); Ph 2b PPV-MF: Bomedemstat 0.6 mg/kg/d -2.3 (-31.5 to 26.9); Ph 2b PET-MF: Bomedemstat 0.6 mg/kg/d 1.2 (-10.9 to 13.2)
Percentage Change From Baseline in Spleen Size (Primary), Mean, Percentage Change: Ph 1/2a PMF: Bomedemstat 0.25 mg/kg/d -36.5 (-68.0 to -5.0); Ph 1/2a PPV-MF: Bomedemstat 0.25 mg/kg/d 9.6 (-95.1 to 114.2); Ph 1/2a PET-MF: Bomedemstat 0.25 mg/kg/d 24.1 (-79.4 to 127.7); Ph 2b PMF: Bomedemstat 0.5 mg/kg/d 20.7 (-132.2 to 173.7); Ph 2b PPV-MF: Bomedemstat 0.5 mg/kg/d -28.1 (-257.8 to 201.6); Ph 2b PET-MF: Bomedemstat 0.5 mg/kg/d 11.0 (-70.7 to 92.7); Ph 2b PMF: Bomedemstat 0.6 mg/kg/d -34.7 (-58.1 to -11.3); Ph 2b PPV-MF: Bomedemstat 0.6 mg/kg/d -38.2 (-53.4 to -23.1); Ph 2b PET-MF: Bomedemstat 0.6 mg/kg/d -59.6 (-113.4 to -5.7)

Adverse events

Time frame: Up to approximately 30 months

Arm	Deaths	Serious adverse events	Other adverse events
Ph 1/2a PMF: Bomedemstat 0.25 mg/kg/d	0/9 (0.0%)	4/9 (44.4%)	9/9 (100.0%)
Ph 1/2a PPV-MF: Bomedemstat 0.25 mg/kg/d	0/3 (0.0%)	2/3 (66.7%)	3/3 (100.0%)
Ph 1/2a PET-MF: Bomedemstat 0.25 mg/kg/d	0/6 (0.0%)	5/6 (83.3%)	6/6 (100.0%)
Ph 2b PMF: Bomedemstat 0.5 mg/kg/d	1/8 (12.5%)	4/8 (50.0%)	8/8 (100.0%)
Ph 2b PPV-MF: Bomedemstat 0.5 mg/kg/d	1/5 (20.0%)	4/5 (80.0%)	5/5 (100.0%)
Ph 2b PET-MF: Bomedemstat 0.5 mg/kg/d	0/11 (0.0%)	7/11 (63.6%)	11/11 (100.0%)
Ph 2b PMF: Bomedemstat 0.6 mg/kg/d	1/24 (4.2%)	12/24 (50.0%)	23/24 (95.8%)
Ph 2b PPV-MF: Bomedemstat 0.6 mg/kg/d	0/11 (0.0%)	3/11 (27.3%)	10/11 (90.9%)
Ph 2b PET-MF: Bomedemstat 0.6 mg/kg/d	0/13 (0.0%)	3/13 (23.1%)	12/13 (92.3%)

Serious adverse events by term

Term	Organ system	Ph 1/2a PMF: Bomedemstat 0.25 mg/kg/d	Ph 1/2a PPV-MF: Bomedemstat 0.25 mg/kg/d	Ph 1/2a PET-MF: Bomedemstat 0.25 mg/kg/d	Ph 2b PMF: Bomedemstat 0.5 mg/kg/d	Ph 2b PPV-MF: Bomedemstat 0.5 mg/kg/d	Ph 2b PET-MF: Bomedemstat 0.5 mg/kg/d	Ph 2b PMF: Bomedemstat 0.6 mg/kg/d	Ph 2b PPV-MF: Bomedemstat 0.6 mg/kg/d	Ph 2b PET-MF: Bomedemstat 0.6 mg/kg/d
Anaemia	Blood and lymphatic system disorders	2/9	0/3	3/6	2/8	2/5	5/11	2/24	2/11	2/13
Splenomegaly	Blood and lymphatic system disorders	0/9	0/3	1/6	0/8	0/5	0/11	0/24	0/11	0/13
Thrombocytopenia	Blood and lymphatic system disorders	2/9	1/3	3/6	4/8	2/5	7/11	1/24	3/11	3/13
Atrial fibrillation	Cardiac disorders	1/9	0/3	0/6	0/8	1/5	1/11	0/24	0/11	0/13
Cardiac failure	Cardiac disorders	0/9	0/3	1/6	0/8	0/5	0/11	0/24	0/11	0/13
Cardiac failure congestive	Cardiac disorders	1/9	0/3	0/6	0/8	0/5	1/11	0/24	0/11	0/13
Cardiopulmonary failure	Cardiac disorders	0/9	0/3	0/6	0/8	0/5	1/11	0/24	0/11	0/13
Palpitations	Cardiac disorders	0/9	0/3	1/6	0/8	0/5	0/11	1/24	0/11	0/13
Supraventricular tachycardia	Cardiac disorders	0/9	0/3	0/6	0/8	0/5	0/11	1/24	0/11	0/13
Vertigo	Ear and labyrinth disorders	0/9	0/3	0/6	0/8	0/5	1/11	0/24	0/11	0/13
Abdominal discomfort	Gastrointestinal disorders	0/9	1/3	1/6	0/8	0/5	1/11	2/24	0/11	0/13
Abdominal pain	Gastrointestinal disorders	0/9	2/3	2/6	0/8	1/5	2/11	1/24	1/11	1/13
Abdominal wall haematoma	Gastrointestinal disorders	0/9	0/3	0/6	0/8	0/5	0/11	0/24	1/11	0/13
Anal haemorrhage	Gastrointestinal disorders	0/9	0/3	0/6	0/8	0/5	0/11	1/24	0/11	0/13
Faecaloma	Gastrointestinal disorders	0/9	0/3	0/6	0/8	0/5	0/11	1/24	0/11	0/13
Gastrointestinal haemorrhage	Gastrointestinal disorders	0/9	0/3	0/6	0/8	0/5	0/11	1/24	0/11	0/13
Hiatus hernia	Gastrointestinal disorders	1/9	0/3	0/6	0/8	0/5	0/11	0/24	0/11	0/13
Inguinal hernia	Gastrointestinal disorders	0/9	0/3	0/6	0/8	0/5	1/11	0/24	0/11	0/13
Nausea	Gastrointestinal disorders	0/9	2/3	3/6	2/8	1/5	2/11	4/24	1/11	1/13
Rectal haemorrhage	Gastrointestinal disorders	0/9	0/3	0/6	1/8	1/5	0/11	0/24	0/11	0/13
Retroperitoneal haemorrhage	Gastrointestinal disorders	0/9	0/3	1/6	0/8	0/5	0/11	0/24	0/11	0/13
Small intestinal haemorrhage	Gastrointestinal disorders	0/9	0/3	0/6	1/8	0/5	0/11	0/24	0/11	0/13
Cholecystitis	Hepatobiliary disorders	0/9	0/3	0/6	0/8	0/5	0/11	1/24	0/11	0/13
Appendicitis perforated	Infections and infestations	0/9	0/3	0/6	0/8	0/5	1/11	0/24	0/11	0/13
Atypical pneumonia	Infections and infestations	0/9	0/3	0/6	0/8	0/5	1/11	0/24	0/11	0/13
Cellulitis	Infections and infestations	1/9	0/3	2/6	0/8	1/5	0/11	1/24	1/11	0/13
Clostridium difficile colitis	Infections and infestations	0/9	0/3	0/6	0/8	0/5	1/11	1/24	0/11	0/13
Diverticulitis	Infections and infestations	1/9	0/3	1/6	0/8	0/5	1/11	0/24	0/11	0/13
Erysipelas	Infections and infestations	0/9	0/3	0/6	0/8	0/5	1/11	0/24	0/11	0/13
Gastroenteritis	Infections and infestations	1/9	1/3	0/6	0/8	0/5	0/11	0/24	0/11	0/13
Gastroenteritis viral	Infections and infestations	1/9	0/3	0/6	0/8	0/5	0/11	0/24	0/11	0/13
Influenza	Infections and infestations	0/9	0/3	0/6	1/8	0/5	0/11	0/24	0/11	0/13
Lower respiratory tract infection	Infections and infestations	2/9	0/3	0/6	0/8	0/5	0/11	0/24	0/11	0/13
Peritonsillar abscess	Infections and infestations	0/9	0/3	0/6	0/8	0/5	0/11	1/24	0/11	0/13
Pneumonia	Infections and infestations	0/9	0/3	0/6	3/8	0/5	2/11	1/24	0/11	1/13
Post procedural cellulitis	Infections and infestations	0/9	0/3	0/6	0/8	0/5	0/11	1/24	0/11	0/13
Renal abscess	Infections and infestations	0/9	0/3	0/6	0/8	1/5	0/11	0/24	0/11	0/13
Respiratory tract infection	Infections and infestations	1/9	0/3	0/6	0/8	0/5	0/11	0/24	0/11	0/13
Sepsis	Infections and infestations	0/9	0/3	0/6	0/8	0/5	0/11	0/24	1/11	1/13
Septic shock	Infections and infestations	0/9	0/3	0/6	1/8	0/5	0/11	0/24	0/11	0/13
Spontaneous bacterial peritonitis	Infections and infestations	0/9	0/3	0/6	0/8	0/5	0/11	0/24	0/11	1/13
Urinary tract infection	Infections and infestations	0/9	0/3	0/6	0/8	0/5	0/11	1/24	0/11	2/13
Hip fracture	Injury, poisoning and procedural complications	0/9	1/3	0/6	0/8	0/5	0/11	0/24	0/11	0/13
Humerus fracture	Injury, poisoning and procedural complications	0/9	0/3	0/6	0/8	0/5	1/11	0/24	0/11	0/13
Post procedural complication	Injury, poisoning and procedural complications	0/9	0/3	0/6	0/8	0/5	1/11	0/24	0/11	0/13
Post-traumatic pain	Injury, poisoning and procedural complications	0/9	0/3	0/6	0/8	1/5	0/11	0/24	0/11	0/13
Toxicity to various agents	Injury, poisoning and procedural complications	0/9	0/3	0/6	0/8	0/5	0/11	1/24	0/11	0/13
Gout	Metabolism and nutrition disorders	0/9	0/3	3/6	0/8	0/5	1/11	1/24	0/11	0/13
Hypervolaemia	Metabolism and nutrition disorders	0/9	0/3	0/6	0/8	0/5	0/11	0/24	1/11	0/13
Arthralgia	Musculoskeletal and connective tissue disorders	2/9	1/3	3/6	0/8	2/5	2/11	3/24	1/11	0/13
Back pain	Musculoskeletal and connective tissue disorders	0/9	0/3	0/6	0/8	1/5	2/11	0/24	1/11	1/13
Myalgia	Musculoskeletal and connective tissue disorders	0/9	0/3	1/6	1/8	1/5	2/11	1/24	0/11	0/13
Cerebrovascular accident	Nervous system disorders	0/9	0/3	0/6	0/8	1/5	0/11	0/24	0/11	0/13
Headache	Nervous system disorders	1/9	0/3	1/6	1/8	2/5	0/11	1/24	0/11	0/13
Syncope	Nervous system disorders	0/9	0/3	1/6	0/8	0/5	0/11	0/24	0/11	0/13
Toxic encephalopathy	Nervous system disorders	0/9	0/3	0/6	0/8	0/5	1/11	0/24	0/11	0/13
Acute kidney injury	Renal and urinary disorders	0/9	0/3	0/6	0/8	1/5	1/11	0/24	0/11	1/13
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	0/9	0/3	0/6	0/8	0/5	0/11	1/24	0/11	0/13
Dyspnoea	Respiratory, thoracic and mediastinal disorders	1/9	0/3	2/6	1/8	1/5	0/11	0/24	0/11	1/13
Pleurisy	Respiratory, thoracic and mediastinal disorders	0/9	0/3	0/6	0/8	0/5	0/11	1/24	0/11	0/13

5 more terms not shown.

Other adverse events by term

Term	Organ system	Ph 1/2a PMF: Bomedemstat 0.25 mg/kg/d	Ph 1/2a PPV-MF: Bomedemstat 0.25 mg/kg/d	Ph 1/2a PET-MF: Bomedemstat 0.25 mg/kg/d	Ph 2b PMF: Bomedemstat 0.5 mg/kg/d	Ph 2b PPV-MF: Bomedemstat 0.5 mg/kg/d	Ph 2b PET-MF: Bomedemstat 0.5 mg/kg/d	Ph 2b PMF: Bomedemstat 0.6 mg/kg/d	Ph 2b PPV-MF: Bomedemstat 0.6 mg/kg/d	Ph 2b PET-MF: Bomedemstat 0.6 mg/kg/d
Anaemia	Blood and lymphatic system disorders	7/9	2/3	5/6	2/8	3/5	5/11	5/24	3/11	3/13
Leukocytosis	Blood and lymphatic system disorders	0/9	0/3	0/6	0/8	0/5	0/11	1/24	0/11	1/13
Leukopenia	Blood and lymphatic system disorders	1/9	1/3	2/6	0/8	0/5	0/11	1/24	1/11	0/13
Lymphadenopathy	Blood and lymphatic system disorders	1/9	0/3	0/6	0/8	0/5	1/11	0/24	0/11	1/13
Lymphopenia	Blood and lymphatic system disorders	0/9	0/3	0/6	1/8	0/5	1/11	0/24	2/11	0/13
Neutropenia	Blood and lymphatic system disorders	1/9	1/3	2/6	1/8	0/5	0/11	3/24	1/11	0/13
Splenomegaly	Blood and lymphatic system disorders	0/9	0/3	1/6	0/8	0/5	0/11	0/24	0/11	0/13
Thrombocytopenia	Blood and lymphatic system disorders	5/9	2/3	4/6	7/8	3/5	8/11	4/24	6/11	4/13
Aortic valve incompetence	Cardiac disorders	0/9	0/3	1/6	0/8	0/5	0/11	0/24	0/11	0/13
Atrial fibrillation	Cardiac disorders	1/9	0/3	0/6	0/8	1/5	1/11	0/24	0/11	0/13
Bradycardia	Cardiac disorders	0/9	0/3	0/6	1/8	0/5	0/11	0/24	0/11	0/13
Cardiac failure congestive	Cardiac disorders	1/9	0/3	0/6	0/8	0/5	0/11	0/24	0/11	0/13
Cardiac valve disease	Cardiac disorders	0/9	0/3	0/6	0/8	0/5	1/11	0/24	0/11	0/13
Cardiomegaly	Cardiac disorders	0/9	0/3	0/6	0/8	0/5	0/11	0/24	0/11	1/13
Myocardial ischaemia	Cardiac disorders	0/9	0/3	0/6	0/8	0/5	0/11	1/24	1/11	0/13
Palpitations	Cardiac disorders	0/9	0/3	1/6	0/8	0/5	0/11	0/24	2/11	0/13
Pericardial effusion	Cardiac disorders	0/9	0/3	0/6	0/8	0/5	0/11	0/24	0/11	1/13
Sinus tachycardia	Cardiac disorders	0/9	0/3	0/6	0/8	0/5	0/11	0/24	1/11	0/13
Ventricular extrasystoles	Cardiac disorders	0/9	0/3	0/6	0/8	0/5	0/11	0/24	0/11	1/13
Ear pain	Ear and labyrinth disorders	1/9	0/3	0/6	0/8	1/5	0/11	0/24	0/11	0/13
Tinnitus	Ear and labyrinth disorders	0/9	0/3	1/6	0/8	0/5	0/11	0/24	0/11	1/13
Blepharitis	Eye disorders	0/9	0/3	0/6	0/8	0/5	0/11	2/24	0/11	0/13
Conjunctival haemorrhage	Eye disorders	0/9	0/3	1/6	0/8	0/5	1/11	0/24	0/11	0/13
Eye oedema	Eye disorders	1/9	0/3	0/6	0/8	0/5	0/11	0/24	1/11	0/13
Ocular hyperaemia	Eye disorders	0/9	0/3	0/6	1/8	0/5	0/11	0/24	0/11	1/13
Photophobia	Eye disorders	0/9	0/3	1/6	0/8	0/5	0/11	0/24	0/11	0/13
Photopsia	Eye disorders	0/9	0/3	0/6	0/8	0/5	0/11	0/24	0/11	1/13
Vision blurred	Eye disorders	0/9	0/3	1/6	0/8	0/5	0/11	0/24	0/11	0/13
Abdominal discomfort	Gastrointestinal disorders	0/9	1/3	1/6	0/8	0/5	1/11	2/24	0/11	0/13
Abdominal distension	Gastrointestinal disorders	1/9	1/3	3/6	1/8	0/5	0/11	0/24	1/11	1/13
Abdominal mass	Gastrointestinal disorders	0/9	1/3	1/6	0/8	0/5	0/11	0/24	0/11	0/13
Abdominal pain	Gastrointestinal disorders	1/9	1/3	2/6	1/8	1/5	2/11	3/24	2/11	2/13
Abdominal pain lower	Gastrointestinal disorders	1/9	0/3	1/6	0/8	1/5	0/11	0/24	0/11	0/13
Constipation	Gastrointestinal disorders	3/9	1/3	0/6	2/8	1/5	6/11	4/24	3/11	1/13
Diarrhoea	Gastrointestinal disorders	4/9	1/3	5/6	3/8	0/5	4/11	9/24	2/11	2/13
Dry mouth	Gastrointestinal disorders	0/9	1/3	0/6	1/8	0/5	0/11	0/24	2/11	0/13
Dyspepsia	Gastrointestinal disorders	0/9	1/3	1/6	0/8	0/5	0/11	0/24	0/11	1/13
Dysphagia	Gastrointestinal disorders	0/9	0/3	0/6	0/8	0/5	1/11	0/24	1/11	1/13
Eructation	Gastrointestinal disorders	1/9	0/3	0/6	0/8	0/5	0/11	1/24	0/11	0/13
Flatulence	Gastrointestinal disorders	0/9	0/3	0/6	0/8	0/5	0/11	0/24	1/11	1/13
Gastrooesophageal reflux disease	Gastrointestinal disorders	1/9	0/3	1/6	0/8	0/5	0/11	0/24	0/11	1/13
Gingival bleeding	Gastrointestinal disorders	0/9	0/3	1/6	0/8	0/5	0/11	1/24	0/11	0/13
Haematochezia	Gastrointestinal disorders	0/9	0/3	0/6	0/8	0/5	1/11	0/24	0/11	0/13
Lip haemorrhage	Gastrointestinal disorders	0/9	0/3	1/6	0/8	0/5	1/11	0/24	0/11	0/13
Lip ulceration	Gastrointestinal disorders	1/9	0/3	0/6	0/8	0/5	0/11	0/24	0/11	0/13
Mouth ulceration	Gastrointestinal disorders	2/9	0/3	0/6	0/8	1/5	0/11	1/24	0/11	0/13
Nausea	Gastrointestinal disorders	0/9	2/3	3/6	5/8	2/5	3/11	7/24	3/11	2/13
Odynophagia	Gastrointestinal disorders	0/9	0/3	0/6	0/8	0/5	0/11	0/24	0/11	1/13
Oral mucosal blistering	Gastrointestinal disorders	0/9	0/3	0/6	0/8	0/5	0/11	0/24	0/11	1/13
Oral pain	Gastrointestinal disorders	0/9	0/3	0/6	1/8	0/5	0/11	0/24	0/11	0/13
Rectal haemorrhage	Gastrointestinal disorders	0/9	0/3	0/6	1/8	0/5	0/11	0/24	0/11	0/13
Retroperitoneal haematoma	Gastrointestinal disorders	0/9	0/3	1/6	0/8	0/5	0/11	0/24	0/11	0/13
Stomatitis	Gastrointestinal disorders	0/9	0/3	1/6	0/8	1/5	0/11	0/24	1/11	0/13
Tongue discolouration	Gastrointestinal disorders	0/9	0/3	0/6	0/8	0/5	0/11	0/24	0/11	1/13
Toothache	Gastrointestinal disorders	1/9	0/3	0/6	0/8	0/5	0/11	0/24	0/11	0/13
Vomiting	Gastrointestinal disorders	0/9	0/3	1/6	2/8	2/5	1/11	2/24	1/11	1/13
Biliary colic	Hepatobiliary disorders	0/9	0/3	0/6	0/8	0/5	1/11	0/24	0/11	0/13
COVID-19	Infections and infestations	0/9	0/3	0/6	2/8	0/5	1/11	1/24	0/11	0/13
Cellulitis	Infections and infestations	1/9	0/3	1/6	0/8	1/5	0/11	3/24	1/11	0/13
Clostridium difficile colitis	Infections and infestations	0/9	0/3	0/6	0/8	0/5	1/11	1/24	0/11	0/13

231 more terms not shown.

+Locations (5)

Facility	City	Country
University of Michigan	Ann Arbor, Michigan	United States
Royal Adelaide Hospital	Adelaide, South Australia	Australia
Universitatsklinikum Essen	Essen	Germany
Azienda Ospedaliero Universitaria Careggi	Florence	Italy
Guy's and St Thomas' Hospitals	London	United Kingdom

+Publications

Results publication: Gill H, Yacoub A, Gerds AT, Shortt J, Rossetti JM, Mead AJ, Gothert JR, Koschmieder S, Ewing J, Halpern AB, Palandri F, Passamonti F, Mesa R, Marchetti M, Harrison C, Vannucchi AM, Watts JM, Wood JC, Ross DM, Peppe J, Natsoulis G, Rienhoff HY Jr. The lysine-specific demethylase 1 (LSD1) inhibitor bomedemstat in myelofibrosis: results from a phase 1/2 study. Blood Adv. 2026 Jul 14;10(13):4585-4594. doi: 10.1182/bloodadvances.2025018141. PMID 42054549
Results publication: Gill H, Palandri F, Ross DM, Gothert JR, Cochrane T, Larsen SR, Halpern AB, Shortt J, Rossetti JM, Liang J, Marchetti M, Wilson AJ, Innes AJ, Hanna M, Vianelli N, Stevenson WS, Vannucchi AM, Kleppe M, Flynn J, Natsoulis G, Harrison CN, Rienhoff HY Jr. Phase 2 study of the lysine-specific demethylase 1 inhibitor bomedemstat for essential thrombocythemia. Blood Adv. 2026 May 26;10(10):3494-3504. doi: 10.1182/bloodadvances.2025017575. PMID 41758981

+Study documents

Study Protocol (PDF, 2020-06-23)
Statistical Analysis Plan (PDF, 2021-11-18)

+Investigators

Medical Director, Study director, Merck Sharp & Dohme LLC

+Funding

NIH grants: 2018

My Notes

Public

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